NGR-hTNF in Combination With Standard Chemotherapy to Treat Patients With Advanced Non-small Cell Lung Cancer

NCT00994097 | Completed Phase 2

• 2 other identifiers: NGR0142008-002703-20
• Study Type: interventional
• Target: 121
• Locations: 1 country
• Sites: 4

Brief Summary

The main objective of this study is to demonstrate superiority in progression-free survival (PFS) when NGR-hTNF is added to standard chemotherapy regimen (cisplatin/gemcitabine or cisplatin/pemetrexed) in locally advanced (stage IIIb with supraclavicular lymph node metastases or malignant pleural or pericardial effusion), metastatic (stage IV) or recurrent non-small cell lung cancer (NSCLC).

Conditions

Non-small Cell Lung Cancer

Keywords

NGR-hTNF; Randomized controlled trial; Gemcitabine; Cisplatin; Pemetrexed; Carcinoma, non-small cell lung

Outcome Measures

Primary Outcomes (1)

• Progression-free survival (PFS)

  PFS evaluated according to Response evaluation criteria in solid tumors (RECIST)

  Every 6 weeks during study treatment and every 6 weeks during the follow-up before PD

Secondary Outcomes (4)

• Safety according to NCI-CTCAE criteria (version 3)

  from the date of randomization until 28 days after last treatment

• Objective response rate

  Every 6 weeks during study treatment and every 6 weeks during the follow-up before PD

• Duration of response (DR)

  from the time of first recorded evidence of complete response or partial response until the progressive disease objectively documented

• Overall survival (OS)

  from the randomization until to the date of patient death or discontinuation from the study

Study Arms (2)

A: NGR-hTNF + cisplatin/gemcitabine or cisplatin/pemetrexed

EXPERIMENTAL

NGR-hTNF with cisplatin/gemcitabine regimen in patients with squamous histology or with cisplatin/pemetrexed regimen in patients with nonsquamous histology

Drug: NGR-hTNF; Drug: Cisplatin; Drug: Gemcitabine; Drug: Pemetrexed

B: cisplatin/gemcitabine or cisplatin/pemetrexed

ACTIVE COMPARATOR

Cisplatin/gemcitabine regimen is administered in patients with squamous histology and cisplatin/pemetrexed regimen is administered in patients with nonsquamous histology

Drug: Cisplatin; Drug: Gemcitabine; Drug: Pemetrexed

Interventions

NGR-hTNF DRUG

NGR-hTNF: 0.8 mcg/m² as 60-minute intravenous infusion every 3 weeks until confirmed evidence of disease progression or unacceptable toxicity occurs

A: NGR-hTNF + cisplatin/gemcitabine or cisplatin/pemetrexed

Cisplatin DRUG

Cisplatin: 80 mg/m² intravenous infusion on day 1 every 3 weeks for a maximum of 6 cycles

A: NGR-hTNF + cisplatin/gemcitabine or cisplatin/pemetrexed; B: cisplatin/gemcitabine or cisplatin/pemetrexed

Gemcitabine DRUG

Gemcitabine: 1,250 mg/m² intravenous infusion on days 1 and 8 every 3 weeks for a maximum of 6 cycles

A: NGR-hTNF + cisplatin/gemcitabine or cisplatin/pemetrexed; B: cisplatin/gemcitabine or cisplatin/pemetrexed

Pemetrexed DRUG

Pemetrexed: 500 mg/m² intravenous infusion on day 1 every 3 weeks for a maximum of 6 cycles

A: NGR-hTNF + cisplatin/gemcitabine or cisplatin/pemetrexed; B: cisplatin/gemcitabine or cisplatin/pemetrexed

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically documented inoperable, locally advanced (stage IIIb with supraclavicular lymph node metastases or malignant pleural or pericardial effusion), metastatic (stage IV) or recurrent NSCLC. Mixed tumors should be categorized according to the predominant cell type.
• Age ≥18 years
• Life expectancy more than 3 months
• ECOG performance status 0-1
• At least one unidimensional measurable lesion (as per RECIST criteria)
• Adequate baseline bone marrow, hepatic and renal function, defined as follows:
• Neutrophils \>1.5 x 10\^9/L and platelets \> 100 x 10\^9/L
• Bilirubin \<1.5 x ULN
• AST and/or ALT \<2.5 x ULN in absence of liver metastasis
• AST and/or ALT \<5 x ULN in presence of liver metastasis
• Serum creatinine \<1.5 x ULN
• Creatinine clearance (estimated according to Cockcroft-Gault formula) ≥ 50 ml/min
• Patients may have had prior therapy providing the following conditions are met:
• Radiation therapy: wash-out period of 28 days
• Surgery: wash-out period of 14 days

You may not qualify if:

• Prior chemotherapy or treatment with another systemic anti-cancer agent (for example monoclonal antibody, tyrosine kinase inhibitor).
• Patients must not receive any other investigational agents while on study
• Patients with myocardial infarction within the last six (6) months, unstable angina, New York Heart Association (NYHA) grade II or greater congestive heart failure, or serious cardiac arrhythmia requiring medication
• Uncontrolled hypertension
• Prolonged QTc interval (congenital or acquired)
• Patient with significant peripheral vascular disease
• History or evidence upon physical examination of CNS disease unless adequately treated (e.g., primary brain tumor, any brain metastasis, seizure not controlled with standard medical therapy, or history of stroke).
• Patients with active or uncontrolled systemic disease/infections or with serious illness or medical conditions, which is incompatible with the protocol
• Known hypersensitivity/allergic reaction or contraindications to human albumin preparations or to any of the excipients
• Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol
• Pregnancy or lactation. Patients - both males and females - with reproductive potential (i.e. menopausal for less than 1-year and not surgically sterilized) must practice effective contraceptive measures throughout the study. Women of child-bearing potential must provide a negative pregnancy test (serum or urine) within 14 days prior to registration.

Sponsors & Collaborators

• AGC Biologics S.p.A.: lead

Study Sites (4)

Istituto Nazionale per la ricerca sul cancro

Genoa, 16132, Italy

Location

Fondazione San Raffaele del Monte Tabor

Milan, 20132, Italy

Location

Istituto Nazionale dei Tumori

Milan, 20133, Italy

Location

Istituto Europeo Oncologico

Milan, Italy

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

tumor necrosis factor-alpha, CNGRC fusion protein, human; Cisplatin; Gemcitabine; Pemetrexed

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic

Study Officials

• Antonio Lambiase, MD

  AGC Biologics S.p.A.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 13, 2009
• First Posted: October 14, 2009
• Study Start: July 1, 2009
• Primary Completion: March 1, 2017
• Study Completion: March 1, 2017
• Last Updated: September 27, 2018

Record last verified: 2018-08

Locations

IT (4)